Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors.
Differentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all-trans retinoic acid (ATRA). Detailed knowledge about DS has remained limited. We present an analysis of the incidence, characteristics, prognostic factors, and outcome of 739 APL patients treated with ATRA plus idarubicin in 2 consecutive trials (Programa Español de Tratamientos en Hematología [PETHEMA] LPA96 and LPA99). Overall, 183 patients (24.8%) experienced DS, 93 with a severe form (12.6%) and 90 with a moderate form (12.2%). Severe but not moderate DS was associated with an increase in mortality. A bimodal incidence of DS was observed, with peaks occurring in the first and third weeks after the start of ATRA therapy. A multivariate analysis indicated that a WBC count greater than 5 x 10(9)/L and an abnormal serum creatinine level correlated with an increased risk of developing severe DS. Patients receiving systematic prednisone prophylaxis (LPA99 trial) in contrast to those receiving selective prophylaxis with dexamethasone (LPA96 trial) had a lower incidence of severe DS. Patients developing severe DS showed a reduced 7-year relapse-free survival in the LPA96 trial (60% vs 85%, P = .003), but this difference was not apparent in the LPA99 trial (86% vs 88%).
Montesinos
Pau
P
Hospital Universitario La Fe, Valencia, Spain.
Bergua
Juan M
JM
Vellenga
Edo
E
Rayón
Chelo
C
Parody
Ricardo
R
de la Serna
Javier
J
León
Angel
A
Esteve
Jordi
J
Milone
Gustavo
G
Debén
Guillermo
G
Rivas
Concha
C
González
Marcos
M
Tormo
Mar
M
Díaz-Mediavilla
Joaquín
J
González
Jose D
JD
Negri
Silvia
S
Amutio
Elena
E
Brunet
Salut
S
Lowenberg
Bob
B
Sanz
Miguel A
MA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D013577:Syndrome; D013997:Time Factors; D014212:Tretinoin / Q000627:therapeutic use*
D018943:Anthracyclines; D014212:Tretinoin